Zhihang Chen¹, Marie-France Penet¹, Sridhar Nimmagadda¹, Cong Li¹, Sangeeta Ray¹, Paul T. Winnard Jr.¹, Dmitri Artemov¹, Kristine Glunde¹, Martin G. Pomper¹, and Zaver M. Bhujwalla^1
1JHU ICMIC Program, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States

Prostate cancer (PCa) is the second leading cause of death from cancer in men in the U.S. The vast majority of men dying of PCa succumb to metastatic androgen-refractory disease. There is therefore a compelling need to find effective treatments for metastatic PCa. In theranostics, noninvasive imaging-based detection of a target is combined with the delivery of a therapeutic payload to the target. Here we are combining prostate-specific membrane antigen (PSMA) based detection of metastatic PCa with a theranostic PSMA-targeted prototype nanoplex carrying multimodality imaging reporters together with small interfering RNA (siRNA) and a prodrug enzyme.

Liya Wang^1,2, Xiaodong Zhong³, Weiping Qian⁴, Hongwei Chen^1,2, Lily Yang⁴, and Hui Mao^1,2
1Radiology, Emory University School of Medicine, Atlanta, GA, United States, ²Center for Systems Imaging, Emory University, Atlanta, GA, United States, ³MR R&D Collaborations, Siemens Healthcare, Atlanta, GA, United States, ⁴Surgery, Emory University School of Medicine, Atlanta, GA, United States

The method of ultrashort echo time (UTE) imaging was developed and tested for obtaining positive?contrast from receptor targeted magnetic nanoparticle MRI probes in molecular imaging of pancreatic tumors in animal models. This work demonstrated that UTE imaging may overcome the limitation of negative contrast?or signal reduction from T2 or T2* weighted methods typically used for imaging of magnetic nanoparticle contrast agents.

Simonetta Geninatti-Crich¹, Diego Alberti¹, Ibolya Szabo¹, Antonio Toppino², Annamaria Deagostino², Paolo Venturello², Nicoletta Protti³, Silva Bortolussi³, Saverio Altieri³, and Silvio Aime^1
1University of Torino, Torino, Italy, ²University of Torino, Italy, ³University of Pavia, Italy

MR guided Boron Neutron Capture Therapy (BNCT) has been performed using an imaging probe containing both Boron and Gd, targeted at tumor cells through overexpressed LDLs receptors.

Giselle Alexandra Suero Abreu¹, Benjamin B Bartelle¹, Orlando Aristizábal¹, Edward J Houston¹, and Daniel H Turnbull^1,2
1Skirbal Institute of Biomolecular Medicine, NYU School of Medicine, New York, New York, United States, ²Radiology Department, NYU School of Medicine, New York, NY, United States

Angiogenesis is a critical feature of tumor growth and metastasis, and endothelial cell activation represents one of its main biomarkers. Molecular imaging represents an unique tool for in vivo visualization of the specific abnormalities underlying tumor development. We utilized novel transgenic mice, Ts-Biotag, that genetically biotinylate developing vascular endothelial cells expressing Tie2, and targeted these cells with multiple avidinated probes to achieve contrast enhancement of vessels involved in angiogenesis in a mouse melanoma model. Ts-Biotag mouse melanomas showed selective labeling of neovasculature and has the potential to provide spatiotemporal information about tumor angiogenesis and its relationship to specific disease stages.

Jamu K. Alford¹, A. Gregory Sorensen¹, Thomas Benner¹, Blaine A. Chronik², William Bradfield Handler², Timothy J Scholl³, Gunjan Madan⁴, and Peter Caravan^1
1Radiology, A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States, ²Physics and Astronomy, The University of Western Ontario, London, ON, Canada, ³Department of Medical Biophysics, The University of Western Ontario, London, ON, Canada, ⁴Siemens Medical Solutions Inc., Malvern, PA, United States

The first direct protein imaging in a human volunteer is presented here. Delta relaxation enhanced MR, (dreMR) exploits the strong magnetic field dependence of slowly tumbling (e.g. bound) paramagnetic contrast agent. A volunteer with a broken finger was imaged after injection of the albumin-targeted contrast agent MS-325. A 1.5T, clinical MRI system outfitted with an electromagnetic insert (dreMR insert) was used acquire T1-weighted images at relaxation fields of 1.35 and 1.65T. The difference between the images shows contrast exclusive to the protein-bound contrast agent and demonstrated increased contrast in the inflamed tissue about the finger fracture.

April M. Chow^1,2, Mingqian Tan³, Darwin S. Gao^1,4, Shu Juan Fan^1,4, Jerry S. Cheung^1,4, Kwan Man⁵, Zheng-Rong Lu³, and Ed X. Wu^1,4
1Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Pokfulam, Hong Kong SAR, China, People's Republic of, ²Medical Physics & Research Department, Hong Kong Sanatorium & Hospital, Happy Valley, Hong Kong SAR, China, People's Republic of, ³Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, United States, ⁴Department of Electrical and Electronic Engineering, The University of Hong Kong, Pokfulam, Hong Kong SAR, China, People's Republic of, ⁵Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong SAR, China, People's Republic of

Liver fibrosis is characterized by an increased amount of fibrin-fibronectin complexes, which may serve as a specific molecular target for contrast-enhanced MRI. In this study, the feasibility of CGLIIQKNEC (CLT1) peptide-targeted nanoglobular contrast agent (Gd-P) for early detection of liver fibrosis through molecular imaging of fibronectin was investigated at 7T in an experimental mouse model of fibrosis. Considerable contrast enhancements were observed and quantified in normal and fibrotic livers using Gd-P and the control non-targeted KAREC peptide nanoglobular contrast agent (Gd-CP) at 0.03mmolGd/kg. Differential enhancements between normal and fibrotic livers were only found for Gd-P. Our results indicate that Gd-P could be used as a fibrin-fibronectin specific MR contrast agent to detect and characterize liver fibrosis at early phase.

Adi Pais¹, Gunanathan Chidambaram², Inbal Biton³, Raanan Margalit¹, David Milstein², and Hadassa Degani^1
1Biological Regulation, Weizmann Institute of Science, Rehovot, Israel, ²Organic Chemistry, Weizmann Institute of Science, Rehovot, Israel, ³Veterinary Resources, Weizmann Institute of Science, Rehovot, Israel

Molecular imaging of novel contrast agents, targeted to the estrogen receptor (ER), composed of Gd-chelate conjugated to estrogen (EPTA-Gd) or tamoxifen (TPTA-Gd), were investigated in vivo. DCE-MRI, applied in mice bearing human breast cancer tumors showed that EPTA-Gd induced a significantly higher enhancement in MDA-ER-positive tumors than in MDA-ER-negative tumors and muscle tissues, indicating specific binding to ER and heterogeneous ER spatial distribution. In contrast, TPTA-Gd showed high enhancement in muscle tissue and lower and similar enhancement in MDA-ER-positive and negative tumors revealing an unknown interaction with muscle components. In conclusion, EPTA-Gd is a potential molecular imaging probe of ER

Alexander R Guimaraes^1,2, Jason L. Gaglia^3,4, Mukesh G. Harisinghani², Christophe Benoist^3,4, Diane Mathis^3,4, and Ralph Weissleder^1
1Center for Systems Biology, Boston, MA, United States, ²Radiology/Massachusetts General Hospital, Division of Abdominal Imaging and Interventional Radiology, Boston, MA, United States, ³Pathology, Harvard Medical School, Boston, MA, United States, ⁴Section on Immunology and Immunogenetics, Joslin Diabetes Center, Boston, MA, United States

The early, insulitic phase of type 1 Diabetes (T1D) is accompanied with leaky microvasculature and a macrophage infiltrate. We have developed and validated a technique based on MRI and magnetic nanoparticles (MNP) to allow indirect quantification and visualization of insulitis in animal models of DM. Our translation and application of this technique to a clinical trial involving 22 subjects reveal that changes in T2 may be a surrogate marker of the leaky vasculature and infiltrate associated with, and that this technique may distinguish and monitor patients in the early, insulitic phase of T1D.

Simonetta Geninatti-Crich¹, Diego Alberti¹, Ibolya Szabo¹, Dario Longo¹, and Silvio Aime^1
1University of Torino, Torino, Italy

A comparison between the efficiency of slowly moving macromolecular MRI imaging probes at 1 and 7 Tesla was carried out using Gd-loaded/LDL (Low Density Lipoproteins) adducts consisting of 250 Gd amphiphilic complexes incorporated in the lipophilic LDL particles. The sensitivity enhancement obtained at 1 Tesla of B16 melanoma cells labeled with Gd-AAZTAC17/LDL adduct is several times higher than that attained at higher fields.

Jonathan Marmurek^1,2, Khaled Nasr³, Elena Vinogradov², Ananth J. Madhuranthakam⁴, John V. Frangioni³, and Robert E. Lenkinski^2
1Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, United States, ²Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States, ³Hematology and Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States, ⁴Global Applied Science Laboratory, GE Healthcare, Boston, MA, United States

We present a high-relaxivity gadolinium-bisphosphonate contrast agent that specifically targets hydroxyapatite, the malignant form of breast cancer microcalcification. The effect of increasing contrast agent concentration on longitudinal relaxation times measured by ultra-short echo time imaging was consistent with a Langmuir adsorption isotherm. High-affinity binding of the bisphosphonate ligand to hydroxyapatite restricts the rotational freedom of the adsorbed contrast agent and results in an apparent relaxivity exceeding 1000 s^-1/mM. This enhancement enables the detection of bound contrast agent at concentrations as low as 1 μM.